Immunity In Social Amoeba Suggests Ancient Beginnings

August 8, 2007 — Finding an immune system in
the social amoeba (Dictyostelium discoideum) is not only surprising but
it also may prove a clue as to what is necessary for an organism to
become multicellular, said the Baylor College of Medicine researcher
who led the research that appears in the journal Science.

Dictyostelium discoideum usually exists as a single-celled organism.
However, when stressed by starvation, the single cells band together to
form a slug that can move. Eventually the slug changes to produce cells
that perform specific functions -- spores and stalks. In this new
report, Dr. Adam Kuspa, chair of biochemistry and molecular biology at
BCM, and his colleagues describe a new kind of cell they dubbed a
"sentinel" cell.

Sentinel cells circulate within the slug, engulfing invading
bacteria and sequestering poisons or toxins, eventually eliminating
these from the slug. These cells often operate through a particular
mechanism in the cells controlled by a Toll/Interleukin-1 Receptor
domain protein (TirA), Kuspa and his team found.

This signaling pathway or a very similar one is present in plants
and animals, he said. Now it has been identified in amoeba. It has not
been found in fungi.

"Amoeba have, in the last 10 years, become appreciated as one of the
four main forms of life in the crown group of eukaryotic
(multicellular) organisms -- plants, animals, fungi and amoeba," said
Kuspa. "What allowed them to become multicellular?"

One way to estimate the characteristics of the organism that went
before those that were multicellular is to look for characteristics
that are present in two, three or all four of these main groups, he
said.

"Those were likely present in the progenitor organism," said Kuspa.
Because three of the four major groups of organisms have this pathway,
"I argue that means that the progenitor of all multicellular organisms
had this pathway. Since that organism was not likely multicellular, it
must have used it as some kind of signaling to respond to bacteria in
the environment."

Looking at it from another point of view, "it's possible that one of
the properties of those (crown) organisms that allowed them to become
multicellular was the ability to distinguish self from non-self -- the
hallmark of an immune system," said Kuspa. "The speculation is that a
requirement of multicellularity is that you develop systems to
recognize pathogens and other non-self cells from yourself."

Kuspa sees two paths for future research in the area. One is to look
for evidence of the same immune mechanism and protein in other kinds of
amoeba. The other is to look at unicellular organisms to determine if
they have this same kind of immune signaling pathway.

"If none of the early diverging organisms that never became
multicellular developed this kind of signaling system, it would subtly
strengthen our argument," he said.

Others who took part in this work include Drs. Guokai Chen and Olga Zhuchenko, both of BCM.